Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Mar 18;2008(5):695-701.
doi: 10.1055/s-2008-1042813.

A Synthesis of the Tricyclic Core Structure of FR901483 Featuring an Ugi Four-Component Coupling and a Remarkably Selective Elimination Reaction

Hirofumi Seike  1 , Erik J Sorensen
Affiliations

A Synthesis of the Tricyclic Core Structure of FR901483 Featuring an Ugi Four-Component Coupling and a Remarkably Selective Elimination Reaction

Hirofumi Seike et al. Synlett. .

Abstract

Three key reactions, an efficient Ugi four-component coupling, a regiospecific, base-mediated elimination reaction, and an intramolecular nitrone/alkene [3+2] cycloaddition, were used to achieve an effective synthesis of the tricyclic molecular framework of the immunosuppressant FR901483. The outcome of a control experiment supports the idea that an internal deprotonation by an alkoxide ion is the origin of the site selectivity observed in the base-induced elimination of hydroxy mesylate 17.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The molecular structure of FR901483 (1)
Figure 2
Figure 2
A concept for achieving a selective alkene synthesis
Scheme 1
Scheme 1
A strategy for constructing the azatricyclic architecture of FR901483 from four simple starting materials
Scheme 2
Scheme 2
The Ugi reaction enables direct syntheses of compounds 6 and 10
Scheme 3
Scheme 3
Synthesis of key intermediate 17
Scheme 4
Scheme 4
Two examples of eliminations by internal bases
Scheme 5
Scheme 5
A regiospecific, base-mediated elimination of hydroxy mesylate 17
Scheme 6
Scheme 6
Completion of tricyclic carbon skeleton of FR901483
See this image and copyright information in PMC

References

    1. This manuscript is based on Chapter 2 of the Ph.D. thesis of Hirofumi Seike, The Scripps Research Institute, 2003. Experimental procedures and characterization data for the new compounds described in this manuscript are available from the corresponding author upon request.

    1. Sakamoto K, Tsujii E, Abe F, Nakanishi T, Yamashita M, Shigematsu N, Izumi S, Okuhara M. J Antibiot. 1996;49:37. - PubMed

    1. This synthesis established the absolute stereochemistry of FR901483: Snider BB, Lin H. J Am Chem Soc. 1999;121:7778.For an earlier model study, see: Snider BB, Lin H, Foxman BM. J Org Chem. 1998;63:6442.

    1. Scheffler G, Seike H, Sorensen EJ. Angew Chem Int Ed. 2000;39:4593. - PubMed
    1. Ousmer M, Braun NA, Ciufolini MA. Org Lett. 2001;3:765. - PubMed
    2. Ousmer M, Braun NA, Bavoux C, Perrin M, Ciufolini MA. J Am Chem Soc. 2001;123:7534. - PubMed

LinkOut - more resources